LU85894A1 - Derives de 1,2,3,4,5,6-hexahydro-azepino (4,5-b) indole leur preparation,composes intermediaires,et leur application en therapeutique - Google Patents

Derives de 1,2,3,4,5,6-hexahydro-azepino (4,5-b) indole leur preparation,composes intermediaires,et leur application en therapeutique Download PDF

Info

Publication number: LU85894A1
Authority: LU; Luxembourg
Prior art keywords: indole; hexahydro; azepino; compound; group
Prior art date: 1985-05-10

Application number

LU85894A

Other languages

English (en)

French (fr)

Inventor

Jean Hannart

Original Assignee

Omnichem Sa

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1985-05-10

Filing date

1985-05-10

Publication date

1986-12-05

1985-05-10 Application filed by Omnichem Sa filed Critical Omnichem Sa

1985-05-10 Priority to LU85894A priority Critical patent/LU85894A1/fr

1986-05-05 Priority to EP86870064A priority patent/EP0203902A3/de

1986-05-08 Priority to JP61105762A priority patent/JPS61263978A/ja

1986-05-09 Priority to US06/861,524 priority patent/US4719208A/en

1986-05-09 Priority to HU861929A priority patent/HU194883B/hu

1986-12-05 Publication of LU85894A1 publication Critical patent/LU85894A1/fr

Links

150000001875 compounds Chemical class 0.000 title claims description 21
238000002360 preparation method Methods 0.000 title claims description 12
230000001225 therapeutic effect Effects 0.000 title description 2
NGUNYFTXLWTSNC-UHFFFAOYSA-N 1,2,3,4,5,6-hexahydroazepino[4,5-b]indole Chemical class C1CNCCC2=C1C1=CC=CC=C1N2 NGUNYFTXLWTSNC-UHFFFAOYSA-N 0.000 title 1
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 83
238000000034 method Methods 0.000 claims description 54
-1 alkyl radical Chemical class 0.000 claims description 52
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 41
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 41
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 28
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 26
238000006722 reduction reaction Methods 0.000 claims description 21
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 18
239000000243 solution Substances 0.000 claims description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
238000009833 condensation Methods 0.000 claims description 14
230000005494 condensation Effects 0.000 claims description 14
238000006467 substitution reaction Methods 0.000 claims description 14
229910052757 nitrogen Inorganic materials 0.000 claims description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
239000007864 aqueous solution Substances 0.000 claims description 10
239000012280 lithium aluminium hydride Substances 0.000 claims description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
235000011121 sodium hydroxide Nutrition 0.000 claims description 9
150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 8
238000010992 reflux Methods 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 7
239000002904 solvent Substances 0.000 claims description 7
150000003512 tertiary amines Chemical class 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
239000003960 organic solvent Substances 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 5
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 claims description 4
229910002056 binary alloy Inorganic materials 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
150000001350 alkyl halides Chemical class 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 3
238000010531 catalytic reduction reaction Methods 0.000 claims description 3
239000003638 chemical reducing agent Substances 0.000 claims description 3
239000000460 chlorine Substances 0.000 claims description 3
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 3
GYFXJYMXYFYIJO-UHFFFAOYSA-N (3,6-dimethyl-1,2,4,5-tetrahydroazepino[4,5-b]indol-5-yl)methanol Chemical compound OCC1CN(C)CCC2=C1N(C)C1=CC=CC=C21 GYFXJYMXYFYIJO-UHFFFAOYSA-N 0.000 claims description 2
FSVOCBHTNQTUKV-UHFFFAOYSA-N (3-ethyl-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indol-5-yl)methanol Chemical compound OCC1CN(CC)CCC2=C1N(C)C1=CC=CC=C21 FSVOCBHTNQTUKV-UHFFFAOYSA-N 0.000 claims description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 claims description 2
WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims description 2
125000000217 alkyl group Chemical group 0.000 claims description 2
150000003934 aromatic aldehydes Chemical class 0.000 claims description 2
230000003542 behavioural effect Effects 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 claims description 2
239000001257 hydrogen Substances 0.000 claims description 2
229910052739 hydrogen Inorganic materials 0.000 claims description 2
239000013067 intermediate product Substances 0.000 claims description 2
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 2
125000002757 morpholinyl group Chemical group 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 claims description 2
125000004193 piperazinyl group Chemical group 0.000 claims description 2
125000003386 piperidinyl group Chemical group 0.000 claims description 2
150000003141 primary amines Chemical class 0.000 claims description 2
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
150000003335 secondary amines Chemical class 0.000 claims description 2
208000009999 tuberous sclerosis Diseases 0.000 claims description 2
150000003254 radicals Chemical class 0.000 claims 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 2
125000001931 aliphatic group Chemical group 0.000 claims 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
239000000825 pharmaceutical preparation Substances 0.000 claims 2
239000004215 Carbon black (E152) Substances 0.000 claims 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
125000003342 alkenyl group Chemical group 0.000 claims 1
238000000280 densification Methods 0.000 claims 1
229930195733 hydrocarbon Natural products 0.000 claims 1
150000002430 hydrocarbons Chemical class 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
239000007858 starting material Substances 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
239000000047 product Substances 0.000 description 70
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
239000012074 organic phase Substances 0.000 description 14
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
239000008346 aqueous phase Substances 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
ZMKPMNLSLLYATH-UHFFFAOYSA-N azepino[4,5-b]indole Chemical compound C1=CN=CC=C2C3=CC=CC=C3N=C21 ZMKPMNLSLLYATH-UHFFFAOYSA-N 0.000 description 6
238000002425 crystallisation Methods 0.000 description 6
230000008025 crystallization Effects 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
UYKZKVIHTBILAK-UHFFFAOYSA-N methyl azepino[4,5-b]indole-5-carboxylate Chemical compound COC(=O)C1=CN=CC=C2C3=CC=CC=C3N=C12 UYKZKVIHTBILAK-UHFFFAOYSA-N 0.000 description 5
239000000203 mixture Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
229910052786 argon Inorganic materials 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000011368 organic material Substances 0.000 description 3
239000002994 raw material Substances 0.000 description 3
239000012429 reaction media Substances 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
230000004083 survival effect Effects 0.000 description 3
ONJLKJRBRSIGLR-UHFFFAOYSA-N (6-methyl-3h-azepino[4,5-b]indol-5-yl)methanol Chemical compound C12=CC=CC=C2N(C)C2=C1C=CNC=C2CO ONJLKJRBRSIGLR-UHFFFAOYSA-N 0.000 description 2
LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
206010021143 Hypoxia Diseases 0.000 description 2
231100000111 LD50 Toxicity 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
230000007954 hypoxia Effects 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
231100001274 therapeutic index Toxicity 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical compound N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 description 2
XPNKEXOHYMOPLU-UHFFFAOYSA-N (3-ethyl-2,4,5,6-tetrahydro-1h-azepino[4,5-b]indol-5-yl)methyl benzoate Chemical compound C1N(CC)CCC(C2=CC=CC=C2N2)=C2C1COC(=O)C1=CC=CC=C1 XPNKEXOHYMOPLU-UHFFFAOYSA-N 0.000 description 1
IATIULMMFCXNAM-UHFFFAOYSA-N (6-methyl-2,3,4,5-tetrahydro-1h-azepino[4,5-b]indol-5-yl)methanol Chemical compound OCC1CNCCC2=C1N(C)C1=CC=CC=C12 IATIULMMFCXNAM-UHFFFAOYSA-N 0.000 description 1
SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
XXSXHNGFYLWHPH-UHFFFAOYSA-N 1,2,3,4,5,6-hexahydroazepino[4,5-b]indol-5-ylmethanol Chemical compound OCC1CNCCC2=C1NC1=CC=CC=C21 XXSXHNGFYLWHPH-UHFFFAOYSA-N 0.000 description 1
FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 description 1
CFTOTSJVQRFXOF-UHFFFAOYSA-N 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole Chemical class N1C2=CC=CC=C2C2=C1CNCC2 CFTOTSJVQRFXOF-UHFFFAOYSA-N 0.000 description 1
IRSVBMMUTNGSQU-UHFFFAOYSA-N 2-(3-ethyl-2,4,5,6-tetrahydro-1h-azepino[4,5-b]indol-5-yl)ethanol Chemical compound OCCC1CN(CC)CCC2=C1NC1=CC=CC=C21 IRSVBMMUTNGSQU-UHFFFAOYSA-N 0.000 description 1
YMQRPXBBBOXHNZ-UHFFFAOYSA-N 2-chloro-1-morpholin-4-ylethanone Chemical compound ClCC(=O)N1CCOCC1 YMQRPXBBBOXHNZ-UHFFFAOYSA-N 0.000 description 1
NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 1
LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
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VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
230000036626 alertness Effects 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
230000000496 anti-anoxic effect Effects 0.000 description 1
238000013459 approach Methods 0.000 description 1
XNDPCVVLPNDZPN-UHFFFAOYSA-N azepino[4,5-b]indol-5-ylmethanol Chemical compound OCC1=CN=CC=C2C3=CC=CC=C3N=C12 XNDPCVVLPNDZPN-UHFFFAOYSA-N 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
238000006480 benzoylation reaction Methods 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000010828 elution Methods 0.000 description 1
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
KCKIKSJECTZLJA-UHFFFAOYSA-N indol-4-one Chemical compound O=C1C=CC=C2N=CC=C12 KCKIKSJECTZLJA-UHFFFAOYSA-N 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
229910000103 lithium hydride Inorganic materials 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
MZTHMBOTDITKER-UHFFFAOYSA-N methyl 6-methyl-3h-azepino[4,5-b]indole-5-carboxylate Chemical compound COC(=O)C1=CNC=CC2=C1N(C)C1=CC=CC=C21 MZTHMBOTDITKER-UHFFFAOYSA-N 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
ISZIQZCZKOFSBT-UHFFFAOYSA-N pyrrolo[2,3-g][1]benzazepine Chemical compound N1=CC=CC=C2C3=NC=CC3=CC=C21 ISZIQZCZKOFSBT-UHFFFAOYSA-N 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
230000000287 tissue oxygenation Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Indole Compounds (AREA)

LU85894A 1985-05-10 1985-05-10 Derives de 1,2,3,4,5,6-hexahydro-azepino (4,5-b) indole leur preparation,composes intermediaires,et leur application en therapeutique LU85894A1 (fr)

Priority Applications (5)

Application Number	Priority Date	Filing Date	Title
LU85894A LU85894A1 (fr)	1985-05-10	1985-05-10	Derives de 1,2,3,4,5,6-hexahydro-azepino (4,5-b) indole leur preparation,composes intermediaires,et leur application en therapeutique
EP86870064A EP0203902A3 (de)	1985-05-10	1986-05-05	1,2,3,4,5,6-Hexahydroazepino[4,5-b]-indolderivate, ihre Herstellung, Zwischenverbindungen und ihre therapeutische Anwendung
JP61105762A JPS61263978A (ja)	1985-05-10	1986-05-08	１，２，３，４，５，６−ヘキサヒドロアゼピノ〔４，５−ｂ〕インド−ル誘導体、その製造法、中間体化合物、および治療におけるそれらの応用
US06/861,524 US4719208A (en)	1985-05-10	1986-05-09	1,2,3,4,5,6-hexahydroazepino(4,5-B)indole derivatives, their preparation, intermediate compounds, and their application in therapeutics
HU861929A HU194883B (en)	1985-05-10	1986-05-09	Process for production of 1,2,3,4,5,6-hexahydroazepin /4,5-b/ indole derivatives and medical preparatives containing such compounds as active substance

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
LU85894A LU85894A1 (fr)	1985-05-10	1985-05-10	Derives de 1,2,3,4,5,6-hexahydro-azepino (4,5-b) indole leur preparation,composes intermediaires,et leur application en therapeutique
LU85894		1985-05-10

Publications (1)

Publication Number	Publication Date
LU85894A1 true LU85894A1 (fr)	1986-12-05

Family

ID=19730464

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LU85894A LU85894A1 (fr)	1985-05-10	1985-05-10	Derives de 1,2,3,4,5,6-hexahydro-azepino (4,5-b) indole leur preparation,composes intermediaires,et leur application en therapeutique

Country Status (5)

Country	Link
US (1)	US4719208A (de)
EP (1)	EP0203902A3 (de)
JP (1)	JPS61263978A (de)
HU (1)	HU194883B (de)
LU (1)	LU85894A1 (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2663935A1 (fr) *	1990-06-27	1992-01-03	Adir	Nouveaux 1,2,3,4,5,6-hexahydroazepino [4,5-b] indoles et 1,2,3,4-tetrahydrobethacarbolines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent.
TWI329111B (en) *	2002-05-24	2010-08-21	X Ceptor Therapeutics Inc	Azepinoindole and pyridoindole derivatives as pharmaceutical agents
US7595311B2 (en) *	2002-05-24	2009-09-29	Exelixis, Inc.	Azepinoindole derivatives as pharmaceutical agents

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CH445512A (de) *	1964-12-03	1967-10-31	Geigy Ag J R	Verfahren zur Herstellung von neuen Indolderivaten
US3525750A (en) *	1966-05-31	1970-08-25	Geigy Chem Corp	1,2,3,4,5,6-hexahydro-azepino(4,5-b) indole derivatives
FR1524830A (fr) *	1966-05-31	1968-05-10	Geigy Ag J R	Nouveaux dérivés de l'indole et leur préparation
JPS5254693Y2 (de) *	1973-02-27	1977-12-10
US4154943A (en) *	1977-12-29	1979-05-15	University Of Vermont	Preparation of vincadifformine
US4362739A (en) *	1981-05-04	1982-12-07	S.A. Omnichem	Pyrrolo(2,3-d)carbazole derivatives, compositions and use

1985
- 1985-05-10 LU LU85894A patent/LU85894A1/fr unknown
1986
- 1986-05-05 EP EP86870064A patent/EP0203902A3/de not_active Withdrawn
- 1986-05-08 JP JP61105762A patent/JPS61263978A/ja active Pending
- 1986-05-09 US US06/861,524 patent/US4719208A/en not_active Expired - Fee Related
- 1986-05-09 HU HU861929A patent/HU194883B/hu not_active IP Right Cessation

Also Published As

Publication number	Publication date
HUT42772A (en)	1987-08-28
HU194883B (en)	1988-03-28
JPS61263978A (ja)	1986-11-21
US4719208A (en)	1988-01-12
EP0203902A2 (de)	1986-12-03
EP0203902A3 (de)	1988-05-18

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